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新型双功能多肽的表达及其药理学作用研究。

Expression of a novel dual-functional polypeptide and its pharmacological action research.

机构信息

State Key Laboratory of Medical Chemical Biology, Key Laboratory for Bioactive Materials of the Ministry of Education, College of Life Science, Nankai University, 300071 Tianjin, China; School of Mental Health, Jining Medical University, Jining, Shandong 272067, China.

State Key Laboratory of Medical Chemical Biology, Key Laboratory for Bioactive Materials of the Ministry of Education, College of Life Science, Nankai University, 300071 Tianjin, China.

出版信息

Life Sci. 2021 Feb 15;267:118890. doi: 10.1016/j.lfs.2020.118890. Epub 2020 Dec 28.

DOI:10.1016/j.lfs.2020.118890
PMID:33359743
Abstract

AIMS

To develop a dual-functional medicine for hypoglycemic and anti-thrombus.

MAIN METHODS

The long-acting glucagon like peptide-1 (5×GLP-1) and nattokinase (NK) were cloned by SOE PCR and gained the GLP-1 and NK fusion polypeptide after transformed into E. coli. Use of mice models for the hypoglycemic and anti-thrombus activity of the fusion polypeptide. Balb/C mice were given the carrageenan by intraperitoneal injection to induce tail thrombus models. Type 2 diabetes mellitus mice model was used to research the hypoglycemic function of the fusion polypeptide.

KEY FINDINGS

Results showed that the fusion polypeptide could significantly prevent thrombus formation after oral administration. Continuous administration for 15 days, fasting blood glucose levels of the experimental group decreased to nearly normal levels.

SIGNIFICANCE

The present study investigated the expression, purification and functional activity of the rolGLP-1 and NK fusion polypeptide, which provided a foundation for further studying the detailed pharmaceutical mechanism and drug development.

摘要

目的

开发一种兼具降血糖和抗血栓功能的药物。

方法

通过重叠延伸 PCR 克隆长效胰高血糖素样肽-1(5×GLP-1)和纳豆激酶(NK),并将其转化到大肠杆菌中获得 GLP-1 和 NK 融合多肽。利用小鼠模型研究融合多肽的降血糖和抗血栓活性。通过腹腔注射角叉菜胶诱导小鼠尾血栓模型,给予 Balb/C 小鼠。使用 2 型糖尿病小鼠模型研究融合多肽的降血糖功能。

主要发现

结果表明,融合多肽经口服给药后能显著预防血栓形成。连续给药 15 天后,实验组的空腹血糖水平降至接近正常水平。

意义

本研究对 rolGLP-1 和 NK 融合多肽的表达、纯化和功能活性进行了研究,为进一步研究其详细的药物作用机制和药物开发提供了基础。

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